The research program proposed consists of four closely related projects designed to investigate interactions of enveloped RNA viruses with cells of the murine immune system. The principal virus to be studied is the mouse lactic dehydrogenase virus (LDV), first detected as a passenger virus in tumor-bearing mice and subsequently isolated as a unique infectious agent that is non-cytopathic and produces a persistent viremia in the animal. The virus appears to replicate only in macrophages but it has profound effects on the immune system. LDV infection has been associated with enhanced antibody response but decreased graft rejection and recent studies by Michaelides and Schlesinger (investigators on this program) showed that acute LDV infection enhanced tumorigenicity whereas chronic infection inhibited tumor formation. Thus, the LDV-infected mouse provides a unique experimental animal for a broad series of immunobiological and virological investigations. The following four specific projects are to be carried out under this program: 1. A study of the replication and host range specificity of LDV. 2. The characterization of infectious, stable LDV-antibody complex. 3. An examination of the state of the lymphoreticular system in LDV-infected mice, 4. An investigation of the immune response elicited in mice infected with LDV. Results from these studies should yield important new information on: (a) fundamental properties of the immune response and the interdependence of cells involved in the murine immune system, (b) the role of persistent viral infections on the animal's ability to mount various types of immune responses, (c) the specificity of viral-host cell inter-actions, and (d) basic properties of stable viral-antibody complexes and mechanisms responsible for their formation.